ReMEDy2

Current Treatment Options for Acute Ischemic Stroke

Each year approximately 800,00 people in the United States experience a stroke, 200,000 of these strokes are recurrent strokes. The overwhelming majority of strokes are ischemic in nature, meaning a blockage of blood flow in/to the brain. Treatment options for ischemic strokes are limited such that approximately 80%* of these patients have no treatment option other than supportive care. DM199 is being studied as a potential therapeutic option to help these patients.

Currently, the only approved therapeutic available to treat acute ischemic stroke patients is Activase® (Alteplase), a tissue plasminogen activator sometimes referred to as “tPA, which is intended to dissolve the clot causing the blockage of blood flow.  However, tPA must be administered within three (3) hours of the onset of stroke symptoms, per its approved label and may not be administered to patients that have a current risk of intracranial hemorrhage (bleeding).

DM199’s Potential Role in Stroke Therapy

DM199 is a recombinant (synthetic) form of a naturally occurring protein called human tissue kallikrein-1 (KLK1). KLK1 is produced primarily in the kidneys, pancreas and salivary glands. KLK1, which is part of the kallikrein-kinin system, plays an important role in the regulation of local blood flow and vasodilation (the widening of blood vessels which decreases blood pressure) in the body, as well as an important role in mitigating inflammation and oxidative stress (an imbalance between potentially damaging reactive oxygen species, or free radicals, and antioxidants in the body). With age, the body’s ability to produce KLK1 may be reduced. KLK1 levels are often low in patients who have experienced a stroke and/or are at risk of a recurrent stroke.

Treatment with DM199 is intended to both improve the physical recovery from an ischemic stroke and reduce the risk for a recurrent stroke. We believe that DM199 works at the level of damaged cerebral tissues to inhibit the inflammation at the site of the blockage, thereby preventing the spread of ischemia (depravation of blood flow) to the surrounding healthy tissue and to improve the overall health of the inner lining (called the endothelium) of cerebral arteries. We believe that DM199 may further reduce the risk of a recurrent stroke as the improvement in the overall health of the endothelium may stimulate the coverage of arterial plaque by local endothelial cells and thereby prevent that plaque from breaking free and causing an additional blockage (stroke).

Why Patients Should Consider Participating in the ReMEDy2 Study

History of Being Safe and Well Tolerated

DM199 therapy is intended to restore normal levels of the KLK1 protein in the body and thereby restore the natural function of the kallikrein-kinin system. In previous clinical trials, including a 91-patient Phase 2 study in acute ischemic stroke, over 250 patients have received over 2,500 doses of DM199 with no serious adverse events attributed to DM199. The most common adverse events have been constipation, nausea, diarrhea and fever, all of which resolved without additional medical treatment. Additionally, forms of KLK1 produced from human urine and animal sources have treated millions of patients in Asia with a similar excellent safety profile.

Intended Improvement in Stroke Recovery

DM199 is an investigational stroke therapy and is intended to improve patients’ potential for full or nearly full physical recovery and reduce risk of death following an acute ischemic stroke.

Intended Reduction of Stroke Recurrence Risk

DM199 may also reduce patients’ risk of suffering a recurrent stroke following the initial stroke. Approximately 25% of strokes are recurrent strokes with the greatest risk of recurrence occurring in the first few weeks following the first stroke. Recurrent strokes tend to be more disabling and fatal.

Phase 2 Clinical Trial Results

Studying a New Approach to Treating Ischemic Stroke

ReMEDy2 is a clinical trial evaluating DiaMedica’s investigational drug, DM199, which is intended to provide a novel, safe and promising new therapy to improve patient physical recoveries after an ischemic stroke and/or reduce the risk of stroke recurrence. Treatment with DM199 may begin up to 24-hours after the onset of stroke symptoms. This treatment window compares favorably to Activase®, or tPA, which must be administered within three (3) hours of the onset of stroke symptoms, per its approved label. Approximately 350 patients will be recruited to participate in the ReMEDy2 clinical trial.

View ReMEDy2 Trial Details View Study Sites

A Potential Revolution in Treating Ischemic Stroke

Clinical studies have shown that low KLK1 levels are associated with stroke and stroke recurrence1. DM199 is an investigational drug designed to restore normal KLK1 levels allowing the body to selectively produce and release two key hormones, nitric oxide (NO) and prostaglandin (PG). These hormones play an important role in the regulation of local blood flow and vasodilation (the widening of blood vessels which decreases blood pressure) in the body, as well as an important role in mitigating inflammation and oxidative stress (an imbalance between potentially damaging reactive oxygen species, or free radicals, and antioxidants in the body). Restoring normal KLK1 levels  may both improve the physical recovery from an ischemic stroke and reduce the risk for a recurrent stroke. We believe that these hormones work at the level of damaged cerebral tissues to inhibit the inflammation at the site of the blockage, thereby preventing the spread of ischemia (depravation of blood flow) to the surrounding healthy tissue and to improve the overall health of the inner lining (called the endothelium) of cerebral arteries. We believe that these hormones may further reduce the risk of a recurrent stroke as the improvement in the overall health of the endothelium may stimulate the coverage of arterial plaque by local endothelial cells and thereby prevent that plaque from breaking free and causing an additional blockage (stroke).

In a previous Phase 2 study of DM199 in 91 ischemic stroke patients, DM199 has shown promise in improving stroke recoveries, reducing the risk of stroke recurrence and reducing death.

1 Annals of Neurology (2011) 70:265-73

Location

The safety and effectiveness of DM199 for the treatment of acute ischemic stroke has not been established and is limited to investigational use only.